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Wnt-Responsive Odontoblasts Secrete New Dentin after Superficial Tooth Injury.
- Source :
-
Journal of dental research [J Dent Res] 2018 Aug; Vol. 97 (9), pp. 1047-1054. Date of Electronic Publication: 2018 Mar 22. - Publication Year :
- 2018
-
Abstract
- The objective of our experiments was to identify new therapeutic strategies to stimulate dentin formation in an adult tooth. To address this objective, we evaluated dentin production in 2 acute trauma models: one involving a pulp exposure and the other involving a superficial dentin injury. Molecular, cellular, and histologic analyses revealed that in response to a severe injury, where the pulp is exposed to the oral cavity, cell death is rampant and the repair response initiates from surviving pulp cells and, to a lesser extent, surviving odontoblasts. When an injury is superficial, as in the case of a dentin injury model, then disturbances are largely confined to pulp tissue immediately underneath the damaged dentin tubules. We found that the pulp remained vital and innervated; primary odontoblasts upregulated HIF1α; and the rate of mineralization was significantly increased. A tamoxifen-inducible Axin2 <superscript>CreERT2/+</superscript> ; R26R <superscript>mTmG/+</superscript> reporter strain was then used to demonstrate that a population of long-lived Wnt-responsive odontoblasts, which secreted dentin throughout the life of the animal, were responsible for depositing new dentin in response to a superficial injury. Amplifying Wnt signaling in the pulp stimulates dentin secretion, and in the dentin injury model, we show that a liposomal formulation of human WNT3A protein passes through dentinal tubules and is capable of upregulating Wnt signaling in the pulp. These data provide strong proof of concept for a therapeutic pulp-capping material to stimulate Wnt signaling in odontoblasts and thus improve the pulp repair response.
- Subjects :
- Animals
Apoptosis
Dentinogenesis drug effects
Disease Models, Animal
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Liposomes
Mice
Odontoblasts drug effects
Staining and Labeling
Tamoxifen pharmacology
Up-Regulation
Wnt3A Protein pharmacology
X-Ray Microtomography
Dental Pulp Exposure metabolism
Dentin injuries
Dentin metabolism
Dentinogenesis physiology
Odontoblasts metabolism
Signal Transduction drug effects
Wnt3A Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1544-0591
- Volume :
- 97
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of dental research
- Publication Type :
- Academic Journal
- Accession number :
- 29566345
- Full Text :
- https://doi.org/10.1177/0022034518763151